Our 01 through 06 year studies of the effects of ethanol consumption on rat hearts have demonstrated that chronic intake of ethanol sequentially produces abnormalities in cardiac ultrastructure; depression of cardiac mitochondrial respiration and myofibrillar ATPase activity; and alterations of the mechanics and hemodynamics of isolated rat hearts. These studies were conducted with animals consuming 10 to 38% of their daily calories as ethanol (equivalent to quantities consumed by moderate chronic alcoholic patients), for periods up to one year, along with a nutritionally adequate diet. In the 07 through 09 years, we propose investigating the reversibility of these structural, metabolic, and functional abnormalities after ethanol is removed from the diet. We will also evaluate the potential role of acetaldehyde in producing the cardiac abnormalities by studying the acute effects of this metabolite on isolated subcellular fractions and isolated heart function, both alone and in combination with ethanol. Further, we propose examining changes in cardiac relaxing system (sarcoplasmic reticulum) Ca ions binding and uptake in alcoholics and after withdrawal. This supplement will extend these observations a) by examination of the phosphorylation of sarcoplasmic reticulum vesicles to possibly relate changes in calcium flux activity with the susceptibility of the sarcoplasmic reticulum to phosphorylation and b) by SDS-electrophoretic study of alcoholic and control rat heart myosin to possibly relate changes in ATPase activity with alterations in the myosin molecule. In addition we will examine activities of mitochondria, myosin ATPase, and sarcoplasmic reticulum Ca ions binding and uptake in control isolated rat hearts perfused with ethanol (65mM) or acetaldehyde (1mM). Elucidation of these mechanisms is pertinent to the pathogenesis and management of alcoholic cardiomyopathy in patients.